rs370155767

Variant names:

• chr15-45378386-C-A
• NM_001482.3:c.68G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-45378386-C-A
• chr15-45378386-C-G
• chr15-45378386-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001482.3(GATM):​c.68G>T​(p.Arg23Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000292 in 1,367,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R23Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: GATM NM_001482.3 missense, splice_region
• Scores: Splicing: ADA: 0.1771
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

Genes affected

GATM (HGNC:4175): (glycine amidinotransferase) This gene encodes a mitochondrial enzyme that belongs to the amidinotransferase family. This enzyme is involved in creatine biosynthesis, whereby it catalyzes the transfer of a guanido group from L-arginine to glycine, resulting in guanidinoacetic acid, the immediate precursor of creatine. Mutations in this gene cause arginine:glycine amidinotransferase deficiency, an inborn error of creatine synthesis characterized by cognitive disability, language impairment, and behavioral disorders. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22596654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATM	NM_001482.3	c.68G>T	p.Arg23Leu	missense_variant, splice_region_variant	Exon 1 of 9	ENST00000396659.8	NP_001473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATM	ENST00000396659.8	c.68G>T	p.Arg23Leu	missense_variant, splice_region_variant	Exon 1 of 9	1	NM_001482.3	ENSP00000379895.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000292 AC: 4 AN: 1367796 Hom.: 0 Cov.: 30 AF XY: 0.00000445 AC XY: 3 AN XY: 674748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000373

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.28	T;T;D
Sift4G	Benign	0.39	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.28
MutPred		0.41		Loss of MoRF binding (P = 0.0199);Loss of MoRF binding (P = 0.0199);Loss of MoRF binding (P = 0.0199);
MVP		0.32
MPC		0.85
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.13
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.18
dbscSNV1_RF	Benign	0.35
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45670584;